Melatonin alleviates meiotic defects in fetal mouse oocytes induced by Di (2-ethylhexyl) phthalate in vitro

Abstract

Di (2-ethylhexyl) phthalate (DEHP), an estrogen-like compound that is a ubiquitous environmental contaminant, has been reported to adversely affect human and mammalian reproduction. Many studies have found that exposure to DEHP during pregnancy perturbs female germ cell meiosis and is detrimental to oogenesis. Previous studies have demonstrated that melatonin (MLT) is beneficial to reproductive endocrinology, oogenesis, and embryonic development as the ability to antioxidative and antiapoptotic. However, whether the meiotic defect of germ cells exposed to DEHP could be rescued by MLT is not clear. Here, we cultured 12.5 days post coitum (dpc) fetal mouse ovaries for 6 days, exposed them to 100 μM DEHP with or without 1 μM MLT in vitro.. The results showed that DEHP exposure induced the abnormal formation of DNA double-strand breaks (DSBs), and inhibited the repair of DSBs during meiotic recombination. In addition, we found defective oocytes were prone to undergo apoptosis. Notably, this defect could be remarkably ameliorated by the addition of MLT via a reduction of the levels of reactive oxygen species and an inhibition of apoptosis. In conclusion, our data revealed that MLT had a protective action against the meiotic deterioration of fetal oocytes induced by DEHP in the mouse in vitro.

Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation

“…Multiple studies have indicated that melatonin grants protective effects on ovarian follicles against the toxicity induced by gonadotoxic agents such as palmitic acid (PA), Di (2-Ethylhexyl) phthalate, and nicotine. [39][40][41][42] Melatonin's proposed protective benefits are based on documentation of inhibition of ER stress, reduction of reactive oxygen species (ROS) levels, and inhibition of apoptosis. Previous literature 26,27 indicated that melatonin significantly decreased the cisplatin-mediated phosphorylation of PTEN, AKT, and translocation of FOXO3a from the nucleus to cytoplasm in primordial oocytes, blocking the activation of primordial follicles in the mouse ovary.…”

Altered morphokinetics in equine embryos from oocytes exposed to DEHP during IVM

“…Interestingly, a recent study reported that melatonin, another antioxidant, also prevented DEHP‐induced oocyte toxicity (Z. Y. Sun et al, ), thus indicating a growing interest in this research area.…”

“…Recently, culture in the presence of 100 µM DEHP was shown to impair progression through meiotic prophase in fetal mouse oocytes, due to ROS‐associated failure to repair double‐strand DNA breaks, and abnormal chromosome recombination (Z. Y. Sun et al, ). However, these studies on oocyte maturation did not assess developmental competence.…”

Melatonin Abrogates the Anti-Developmental Effect of the AKT Inhibitor SH6 in Bovine Oocytes and Embryos

“…The higher oxygen concentration under the in vitro maturation environment leads to production of high concentrations of ROS which can have detrimental effects on developing embryos [31]. Moreover, the antioxidant activity of melatonin improved the quality of the inferior oocytes [32] in addition to the protective role against certain cytotoxic compounds during IVM process [33,34,35,36]. Also, melatonin alleviated the meiotic defects in fetal mouse oocytes [33] and reduced the apoptosis and oxidative stress in bovine ovarian granulosa cells [37].…”

“…Moreover, the antioxidant activity of melatonin improved the quality of the inferior oocytes [32] in addition to the protective role against certain cytotoxic compounds during IVM process [33,34,35,36]. Also, melatonin alleviated the meiotic defects in fetal mouse oocytes [33] and reduced the apoptosis and oxidative stress in bovine ovarian granulosa cells [37]. Though, the possible mechanisms regarding how melatonin improves and rescues the quality and the developmental potential of oocytes have not been fully defined.…”